Edward T.H. Yeh, M.D. 1980, University of California, Davis UT M. D. Anderson Cancer Center Cardiology Contact Information

Research Interests: Regulation of SUMO and NEDD8 modification; Stem Cell Transplant for Cardiovascular Diseases

Ubiquitination plays a central role in the biology of cells. Our laboratory has discovered two families of ubiquitin-like proteins (SUMO/Sentrin and NEDD8), which defined novel protein modification pathways distinct from ubiquitination. These new pathways also play critical roles in cell cycle progression, signal transduction, and in cell death protection. Our laboratory has a comprehensive program in defining the biology of these pathways and in applying this basic knowledge to clinically relevant disease processes. In addition, my laboratory pioneered in using peripheral blood stem cells to regenerate damaged heart tissues. We have developed in vivo and in vitro models to investigate the mechanism of cell fusion that leads to the regeneration of cardiomyocytes. A student may choose between these two broad areas of innovative research.
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Kamitani T, Nguyen HP, Yeh ETH (1997) Preferential modification of nuclear proteins by a novel ubiquitin-like molecule. J Biol Chem 272:14001-14004.

Gong L, Kamitani T, Fujise K, Caskey L, Yeh ETH (1997) Preferential interaction of sentrin with a ubiquitin-conjugating enzyme, Ubc9. J Biol Chem 272:28198-28201.

Kamitani T, Katsumi K, Nguyen R, Yeh ETH (1997) Characterization of NEDD8, a developmentally down-regulated ubiquitin-like molecule. J Biol Chem 272:28557-28562.

Patel S, Thiagarajan R, Willerson JT, Yeh ETH (1998) Inhibition of alpha-4 integrin and ICAM-1 markedly attenuate macrophage homing to the atherosclerotic plaques in apo-E deficient mice. Circulation 97:75-81.

Kamitani T, Nguyen R, Katsumi K, Fukuda-Kamitani Y, Yeh ETH (1998) Covalent modification of PML by members of the sentrin family of ubiquitin-like proteins. J Biol Chem 273:3117-3120.

Kamitani T, Katsumi K, Nguyen H, Fukuda-Kamitani T, Yeh ETH (1998) Identification of three major sentrinization sites in PML. J Biol Chem 283:26675-26682.

Gong L, Yeh ETH (1999) Identification of the activating and conjugating enzymes of the NEDD8-conjugation pathway. J Biol Chem 274:12036-12042.

Pasceri V, Yeh ETH (1999) A tale of two diseases: atherosclerosis and rheumatoid arthritis. Circulation 100:2124-2126.

Gong LM, Millas S, Maul GD, Yeh ETH (2000) Differential regulation of sentrinized proteins by a novel sentrin-specific protease. J Biol Chem 275:3355-3359.

Pasceri V, Wu DH, Willerson JT, Yeh ETH (2000) Inhibition of vascular inflammation in vitro and in vivo by PPAR-gamma agonists. Circulation 101:235-238.

Gong L, Kamitani T, Millas S, Yeh ETH (2000) Identification of a novel protease with dual specificity for ubiquitin and NEDD8. J Biol Chem 275:14212-14216.

Pasceri V, Willerson JT, Yeh ETH (2000) Direct proinflammatory effects of C-reactive protein on burnan endothelial cells. Circulation 102:2165-2168.

Yeh ETH, Gong L, Kamitani T (2000) Ubiquitin-like proteins - new wines in new bottles. Gene 248:1-14.

Pasceri V, Cheng J, Willerson JT, Yeh ETH (2001) Modulation of C-reactive protein-mediated MCP-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation 103:2531- 2534.

Kamitani T, Kito K, Fukuda-Kamitani T, Yeh ETH (2001) Targeting of NEDD8 and its conjugates for proteasomal degradation by Nub1. J Biol Chem 276:46655-46660.

Yeh ETH, Anderson HV, Pasceri V, Willerson JT (2001) C-reactive protein: Linking inflammation to cardiovascular complication. Circulation 104:974-975.

Pasceri, V., Wu, D.H., Willerson, J.T., Yeh, E.T.H. Modulation of vascular inflammation in vitro and in vivo by PPAR g agonists. Circulation, 101:235-238, 2000.

Gong, L., Kamitani, T., Millas, S., Yeh, E.T.H. Identification of a novel protease with dual specificity for ubiquitin and NEDD8. Journal of Biological Chemistry, 275:14212-14216, 2000.

Wada, H., Yeh, E.T.H., Kamitani, T. A dominant-negative UBC12 inhibits NEDD8 conjugations in vivo. Journal of Biological Chemistry, 275:17008-17015, 2000.

Fujise, K., Zhang, D., Liu, J.L.,Yeh, E.T.H. Regulation of apoptosis and cell cycle progression by MCl-1: Differential Role of PCNA. Journal of Biological Chemistry, 275:39454-39468, 2000.

Kito, K., Yeh, E.T.H., Kamitani, T. Nub1, a Nedd8-interacting protein, is induced by interferon and down-regulates the Nedd8 expression. Journal of Biological Chemistry, 276:20603-9, 2001.

Pasceri, V., Cheng, J., Willerson, J.T., Yeh, E.T.H. Modulation of C-reactive protein-mediated MCP-1 induction in human endothelial cells by anti-atherosclerosis drugs. Circulation, 103:2531-2534, 2001.

Tanaka, T., Kawashima, H., Yeh, E.T.H., Kamitani, T. Regulation of NEDD8 conjugation system by a splicing variant, NUB1L. Journal of Biological Chemistry, 278:32905-32913, 2003.

Calabro, P., Willerson, J.T., Yeh, E.T.H. Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells, Circulation, 108:1930-1932, 2003.

Yeh, E.T.H., Zhang, S., Wu, H.D., Körbling, M., Willerson, J.T., Estrov, Z., Transdifferentiation of human peripheral blood CD34 enriched population into cardiomyocytes, endothelial cells, and smooth muscle cells in vivo, Circulation, 108:2070-2073, 2003.

Cheng, J., Wang, D., Wang Z., Yeh, E.T.H. SENP1 enhances androgen receptor-dependent transcription through desumoylation of HDAC-1, Molecular and Cellular Biology, 24, 6021-6028, 2004.

Yeh, E.T.H ., Tong, A., Lenihan, D.J., Yusuf, S.W., Swafford, J., Champion, C., Durand, J.B., Gibbs, H., Zafarmand, A., Ewer, M. Cardiovascular Complications of Cancer Therapy: Diagnosis, Pathogenesis, and Management. Circulation, 109:3122-3131, 2004.

Calabro, P., Samudio, I., Willerson, J.T., Yeh, E.T.H. Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase ½ and phosphatidylinositol 3-kinase pathways. Circulation, 110:3335-3340, 2004.

Zhang, S., Wang, D., Estrov, Z., Raj, S., Willerson, J.T., Yeh, E.T.H. Both cell fusion and transdifferentiation account for the transformation of human peripheral blood CD34-positive cells into cardiomyocytes in vivo. Circulation, 110:3803-3807, 2004.

Cheng, J., Perkins, N.D., Yeh, E.T.H. Differential Regulation of c-Jun-dependent Transcription by SUMO-specific Proteases. Journal of Biological Chemistry, 280:14492-14498, 2005.

Gong, L., Yeh, E.T.H. Characterization of a family of nucleolar SUMO-specific proteases with preference for SUMO-2 or SUMO-3. Journal of Biological Chemistry, 281(23):15869-77, 2006.

Cheng, J., Bawa, T., Lee, P., Gong, L. Yeh, E.T.H. Role of Desumoylation in the Development of Prostate Cancer. Neoplasia, 8(8):667-676, 2006.

Gao, F., Cheng, J., Shi, T., Yeh, E.T.H. NEDDylation of a Breast Cancer-associated Protein Recruits a Class III Histone Deacetylase that Represses NF k B-dependent Transcription. Nature Cell Biology, 8(10):1171-1177, 2006.

Zhang, S., Shpall, E., Willerson, J.T. Yeh, E.T.H. Fusion of Human Hematopoietic Progenitor Cells and Murine Cardiomyocytes is Mediated by α4β1/VCAM-1 Interaction. Circulation Research, 100:693-702, 2007.

Cheng, J., Kang, X., Zhang, S., Yeh, E.T.H. SUMO-specific protease 1 is essential for stabilization of HIF1α during hypoxia. Cell, 131:584-595, 2007.

Bawa-Khalfe, T., Cheng, J., Wang, Z., Yeh, E.T.H. Induction of the SUMO-specific protease 1 transcription by the androgen receptor in prostate cancer cells. Journal of Biological Chemistry, 282(52):37341-37349, 2007.

Program Affiliation:
Program in Molecular Pathology
Vascular Biology